1. Field of Invention
The present invention relates to biostatic compositions, as well as coatings and methods for preparing biostatic articles using the same.
2. Description of Prior Art
There have been numerous attempts to concentrate antimicrobial, antiseptic or antibiotic agents on the surface of biomaterials or medical devices as a means of reducing the probability of bacterial adhesion and subsequent bacterial infection. Several approaches have been undertaken including (1) the entrapment of active compounds or agents in surface coatings containing polymer layers or matrices, (2) the coupling of active agents to surface polymers or coatings via ionic or other electrostatic forces and (3) the covalent or chemical bonding of active agents to the surface of polymers or materials.
The first approach involves mechanically entrapping agents within a polymer matrix. The agents are generally released by two mechanisms including (a) the dissolution of the polymer material or (b) diffusion of the agent as a result of osmosis. The second approach involves the coupling of agents to polymer materials as a result of an ionic bond or other intermolecular forces of attraction. Intermolecular attractive forces include dipole-dipole, London or dispersion forces, or hydrogen bonding. These attractive forces occur as a result of the electronegativity or charge differences between the polymer molecule and the active agent or agents. The mechanism of release involves desorption of the active agent or agents from the polymer matrix. The third approach involves the covalent binding of agents to polymers surfaces. This includes the joining of the two materials as a result of chemical bond formation. Covalent bonding of antimicrobial agents to polymer matrices affords systems which generally do not release the bound or joined agent under normal physiological conditions. If release of the agent does occur, it is generally as a result of the hydrolysis of a chemical bond.
Attempts have been made to use the first approach by mechanically entrapping agents in a polymer matrix. For example, U.S. Pat. No. 4,603,152 to Laurin and Stupar discloses antimicrobial compositions comprising 30 to 85% polymeric binder and 15 to 70% antimicrobial metal agents or mixtures. The antimicrobial agents form a chain-like structure which releases itself into solutions to create an initial dosage and then provides the pathway for further release of the agents.
U.S. Pat. No. 5,019,096 to Fox et al. relates to a method for preparing an infection-resistant material or medical device comprised of biomedical polymers and an effective amount of antimicrobial agents such as chlorhexidine salts and silver salts. The agents are released in a controlled fashion when the infection-resistant material is in contact with fluids.
U.S. Pat. No. 5,133,090 to Modak and Sampath discloses an antiviral glove which is comprised of an elastomeric material with an inner coating comprised of a chlorhexidine salt and a lubricating agent which delivers the antiinfective agent within 10 minutes of exposure to an aqueous solution.
U.S. Pat. No. 4,853,978 to Stockum and Surgicos is directed to an antimicrobial medical glove possessing an inner coating comprised of a slow releasing antimicrobial agent in a cross-linked starch. The coating affords slow-release of the antimicrobial agent or agents in order to maintain a bacteria-free environment.
The above patents are directed to dissolution or diffusion of the antimicrobial agent into solution.
The second approach mentioned above involves the coupling of agents to polymer materials as a result of the electrostatic interaction of compounds with polymer materials. For example, U.S. Pat. No. 4,769,013 to Lorenz and Creasy relates to materials containing an antimicrobial agent complexed with polyvinylpyrrolidone, which has been rendered insoluble by being complexed with polyurethane. The medical material is capable of releasing the antimicrobial agent upon contact with water.
U.S. Pat. No. 4,381,380 to LaVeen et al. is directed to a thermoplastic polyurethane article treated with iodine for antibacterial use. The polymeric composition is comprised of a partially crosslinked polyurethane which has been complexed with iodine.
Other attempts have been made to use the second approach. U.S. Pat. No. 4,539,239 to Sakamoto and Takagi discloses the use of chemically bound ion-exchange groups, which serve to ionically bind active agents to the surface of biomaterials. This patent also relates to a process for producing a urinary catheter having film forming materials which possesses functional groups capable of being converted into ion-exchange groups. The ion-exchange groups, described as carboxylic acids, then ionically bind with antimicrobial agents. These materials serve to release the agent into surrounding media as a result of changes in external media.
With this second approach, the active agents are bound somewhat loosely via Van der Waals or ionic forces and are readily released into surrounding environments when in contact with solutions.
Attempts have also been made to use the third approach mentioned above to achieve covalent bonding of agents to polymer surfaces. U.S. Pat. Nos. 4,973,493, 5,263,992, and 5,002,582 to Guire and Guire et al. disclose polymers, surfaces and devices which are modified with biocompatible agents, including antimicrobial compounds, whereby the polymer is chemically bound to a surface or device via a chemically linking moiety which is responsive to a photochemical stimulus and whereby the antimicrobial agent is covalently bound to the surface via a different reactive group. The different reactive group is not responsive to the photochemical stimulus. The antimicrobial agents used in these patents include penicillin and lysozyme.
The solid surface and the antimicrobial agent are chemically joined in U.S. Pat. No. 5,263,992 as in the following formula: A-X-B; wherein A is a photochemically responsive group such as a nitrophenylazide derivative or a benzylbenzoyl derivative, X is a linking moiety such as C.sub.1-C.sub.10 alkyl group and B is a thermochemically reactive group such as a nitrophenylhalides, alkylamines, alkylcarboxyls, alkylthiols, alkylaldehydes, alkylmethylimidates, alkylisocyanates, alkylisothiocyanates and alkylhalides. Lysozyme is an enzyme (protein) which dissolves the bacterial cell wall mucopolysaccharides by hydrolyzing the .beta.(1.fwdarw.4) linkages between N-acetyl-D-muramic acid and 2-acetylamino-2-deoxy-D-glucose residues. Penicillin is a broad spectrum .beta.-lactam antibiotic which inhibits bacterial cell wall synthesis. The above patents, however, require the use of photochemically reactive groups.
In contrast, the present invention provides a polymer-bound antimicrobial moiety which when applied to a surface of an article reduces the probability of microorganism adherence and thus the possibility of infection without the use of photochemical stimulus. The polymer-bound antimicrobial moiety does not release the antimicrobial agent into solution and does not reduce the antimicrobial properties of the antimicrobial agent below its capability of acting as a biostatic agent.
For a better understanding of the present invention, together with other and further objects, reference is made to the following description taken in conjunction with the examples, the scope of which is set forth in the appended claims.